BDNF Promotes the Survival of Rat Sensory Epithelial Cells Via the PI3K/Akt and NF-􀀂B/Bcl-2 Signaling Pathways

Abstract

Sensory epithelial cells in the organ of Corti survive throughout life. However, factors for sensory epithelial cell survival are poorly understood at the present time. Here we demonstrated that brain-derived neurotrophic factor (BDNF), a factor committing to neuronal survival, promotes the survival of sensory epithelial cells (OC1) through phos- phatidylinositide 3'-OH kinase (PI3K)/protein kinase B (Akt) and/or nuclear factor kappa B (NF- B)/B cell lymphoma 2 (Bcl-2) pathways. BDNF activated PI3K/Akt kinases and increased NF-B/Bcl-2 activity or expression in association with the survival of OC1 cells in vitro. LY294002, a specific inhibitor for PI3K, and pyrrolidine dithiocarbamate (PDTC), an inhibitor for NF-B, abrogated the protective effect of BDNF on OC1 cells, causing the increased expression of caspase 3 and the apoptotic cell numbers in vitro. Similarly, a dominant negative mutant of I kappa B alpha (I BM, a specific inhibitor of NF-B) abrogated the protective effect of BDNF on OC1 cells. The data demonstrate that BDNF promotes the survival of sensory epithelial cells through the PI3K/Akt and NF- B/Bcl-2 signaling pathways.